Prevalence and risk factors of hepatitis C infection after cardiac surgery in childhood before and after blood donor screening.

BACKGROUND: Since 1974, the risk of acquiring non-A non-B hepatitis by blood transfusion is well known. In 1999, children having had polytransfusions (group 1) after cardiac surgery prior to the establishment of routine blood donor screening could be identified as a risk group for hepatitis C (HCV) infection. PATIENTS AND METHODS: In 1991, Germany began screening blood donors for hepatitis C. To describe the risk after the implementation of blood donor screening, we studied 211 children (group 2) having had open heart surgery after 1991 and compared prevalence for anti-HCV antibodies and known risk factors to group 1. RESULTS: None of the 211 patients with cardiac surgery after 1991 had detectable anti-HCV antibodies, compared to 67 of the 458 patients (14.6%) of group 1 (p < 0.001). The mean number of operations in both groups was virtually the same (mean 1.7 +/- 0.9 in group 1, mean 1.6 +/- 0.9 in group 2, p = 0.075), whereas the total number of blood products per patient differed significantly (group 1 mean 8 +/- 17.6, group 2 mean 3.5 +/- 2.8; p < 0.001). Multivariate analysis of risk factors demonstrates affiliation to group 1, transfusion of fresh blood, warm whole blood, heparinized blood (p < 0.001) and plasma (p = 0.004) as significant. CONCLUSION: After the implementation of blood donor screening, the risk for HCV infection after cardiac surgery in childhood dropped significantly from 14.6% to < 0.5%. These data show the necessity of HCV screening for patients at risk (operations before 1991) and do not favor a general screening for all patients.

Immunogenicity and safety of a virosomal hepatitis A vaccine (Epaxal) in healthy toddlers and children in Chile.

UNLABELLED: In this open study, 20 toddlers and 80 schoolchildren received an intramuscular dose of Epaxal and a booster dose 12 mo later to assess the efficacy and safety of this aluminium-free, virosomal hepatitis A vaccine. Four weeks after primary vaccination, 94% of toddlers and 99% of schoolchildren had seroconverted, and all toddlers and 94% of schoolchildren remained seroprotected for 12 mo. CONCLUSION: After vaccination with Epaxal and booster, all subjects were seroprotected. Epaxal was very well tolerated by both age groups.

[Hepatitis B and C infection in late repatriates]. / Hepatitis B und C bei Spätaussiedlern.

105 late repatriates returning to Germany mostly from Russia, Ukraine and Kazakhstan were tested for present or past viral hepatitis B and 97 of them also for hepatitis C. Anti-HBc was found in 20% (95%-CI: 12,3-31,6%) and Anti-HCV in 3% (95%-CI: 1,3-8,0%) of tested individuals. 5% of tested persons were positive by PCR for HBV-DNA or HCV-DNA and therefore probably source of infection forthese viruses. All PCR positive individuals were not aware of their infection. Prevalence of hepatitis B and C infection was significantly higher than in the general population of Germany. Testing for viral hepatitis Band C should be offered to all late repatriates returning from areas with elevated prevalence of parenterally transmitted viral hepatitis. Further monitoring of the prevalence of viral hepatitis should be done in this group.

Prevalence of GB virus C/hepatitis G virus RNA and anti-E2 glycoprotein antibodies in homosexual men with HIV coinfection.

BACKGROUND: The objective of this cross-sectional, nonrandomized, prospective study was to generate data on the prevalence of GB virus C (GBV-C)/hepatitis G virus (HGV) in a cohort of HIV-infected homosexuals from Munich. PATIENTS: A total of 71 HIV-infected homosexual men were analyzed for prevalence of GBV-C RNA and antibodies to the E2 envelope glycoprotein (E2Ab). 475 healthy volunteer blood donors in southern Bavaria served as a control group. RESULTS: The prevalence of GBV-C RNA was 27% (control group: 2.3%) and the prevalence of E2Ab was 35% (control group: 6%). The total prevalence for present and past infection was 62%. The differences between the HIV-infected patients and the control group were significant (p < 0.0001). GBV-C RNA and E2Ab were not detected simultaneously in any serum sample. The E2Ab positive patients were older than the GBV-C RNA positives (mean 46 years versus 39 years, p = 0.0350). The GBV-C RNA and E2Ab negative patients were older than the GBV-C RNA positives (mean 47 years versus 39 years, p = 0.0236). The E2Ab positive patients had suffered sexually transmitted diseases more frequently than the patients negative for markers of GBV-C infection (p = 0.0308). E2Ab positive patients also had higher mean levels of alanine aminotransferase compared to patients without evidence of GBV-C infection (p = 0.0164). 59.4% of all individuals were anti-HBc IgG positive. CONCLUSION: The data can be interpreted as indirect evidence for sexual transmission of GBV-C.

Role of hepatitis E and other hepatotropic virus in aetiology of sporadic acute viral hepatitis: a hospital based study from urban Delhi.

Major hepatotropic virus continues to be an important cause of acute viral hepatitis (AVH) in developing countries like India. While epidemics of AVH have been well studied few serious sporadic cases from developing countries have been reviewed. We studied prospectively 75 cases of sporadic AVH who reported to our hospital and were evaluated for the presence of various hepatotropic viruses. The seroprevalence of IgG anti-HEV antibodies was studied in the general population as a control. We found 53.3% (40/75) of sporadic AVH cases were due to hepatitis E virus while 11% (8/75) were due to hepatitis B virus. Hepatitis C virus was responsible for 8% (6/75) of the sporadic AVH cases and hepatitis A was found in 5% (4/75) of the cases. No causative agent was found in 23% (17/75) of the sporadic AVH cases. The sporadic AVH cases due to HEV were not clinically or biochemically not different from AVH due to other viruses. We found a high prevalence of IgG anti-HEV in 35.6% (178/500) among the general population of urban Delhi. The study suggested that hepatitis E was the most common cause of sporadic AVH in urban Delhi. High seroprevalence of IgG anti-HEV antibodies in the general population and amongst the sporadic AVH cases suggests that it is unlikely to be protective antibody. IgM anti-HEV positive serology is considered diagnostic of acute hepatitis E infection in India, where hepatitis E is endemic.

Prevalence and clinical outcome of hepatitis C infection in children who underwent cardiac surgery before the implementation of blood-donor screening.

BACKGROUND AND METHODS: There are few data on the prevalence and clinical outcome of hepatitis C infection in children. We studied 458 children who underwent cardiac surgery in Munich, Germany, before 1991, when blood-donor screening for hepatitis C was introduced in Germany. Their mean age at first operation was 2.8 years; none of the children had received blood transfusions before or 'after cardiac surgery, and none of their mothers had antibodies to the hepatitis C virus (anti-HCV). We compared these patients with 458 control subjects matched for age and sex. RESULTS: Sixty-seven (14.6 percent) of the 458 patients who had undergone cardiac surgery had anti-HCV, as compared with 3 (0.7 percent) of the control subjects (P<0.001). At a mean interval of 19.8 years after the first operation, 37 (55 percent) of the 67 patients who were positive for anti-HCV had detectable HCV RNA in their blood. The infection had cleared in the other 30 patients, as evidenced by negative results on three polymerase-chain-reaction analyses performed at six-month intervals. Only 1 of the 37 patients who were positive for HCV RNA had elevated levels of liver enzymes; that patient had severe right-sided congestive heart failure. Of the 17 patients who underwent liver biopsies, only 3 had histologic signs of progressive liver damage. These three patients had additional risk factors: two had congestive heart failure, and the third had also been infected with hepatitis B virus. CONCLUSIONS: Children who had undergone cardiac surgery in Germany before the implementation of blood-donor screening for hepatitis C had a substantial risk of acquiring the infection. However, after about 20 years, the virus had spontaneously cleared in many patients. The clinical course in those still infected seems more benign than would be expected in people infected as adults.

Hepatitis E in Damascus, Syria.

A hospital-based study of acute hepatitis was conducted in Damascus, Syria, from 1995 to 1998. One hundred ninety-three sera from defined acute hepatitis cases were screened by ELISA for IgM anti-HAV, HBsAg, IgM anti-HBc and anti-HCV. Serum samples negative for all markers indicating recent infection by hepatitis A, B, or C were tested for HEV markers. Overall, 47 cases (24.4%) had no detectable hepatitis markers (non-A-E). HAV infection was detected in 71.2% of all viral hepatitis cases. Acute hepatitis B and C constituted 24 and 1.4% of the cases, respectively. Only five cases of acute hepatitis E were noted. Of 47 patients who had non-A-E hepatitis, fifteen (31.9%) tested positive for IgG anti HEV. This study provides indirect evidence that HEV is very likely to be endemic in Damascus, Syria. It reports for the first time the occurrence of hepatitis E in the country, a health problem that should be investigated further.

Quality control study on the performance of GB virus C/hepatitis G virus PCR.

BACKGROUND/AIMS: A novel virus, GBV-C/HGV, with a genome RNA organization similar to that of the Flaviviridae family was identified in sera of patients with hepatitis. The presence of GBV-C/HGV RNA can only be determined by the amplification of genomic regions using the reverse transcriptase-polymerase chain reaction (RT-PCR). METHODS: To assess the quality of the RT-PCR, 14 laboratories investigated a coded serum panel that comprised three GBV-C/HGV RNA-positive sera from three different patients, dilutions of these sera, and three GBV-C/HGV RNA-negative serum samples, two of which were collected from patients with hepatitis C but without GBV-C/HGV infection. In-house RT-PCR as well as commercially available GBV-C/HGV test kits were used in this study. RESULTS: Only four laboratories (29%) reported the expected results, and four laboratories (29%) false-positive results; nine laboratories (64%) reported at least one false-negative result. Eleven laboratories (79%) detected the undiluted samples. The majority of false results were obtained with the dilutions of GBV-C/HGV RNA-positive samples. Negative results in the 10(-4) dilution were not considered to be false-negative, since during pre-screening GBV-C/HGV RNA had been detected in this dilution in only 50% of assays by the three laboratories involved in organizing the evaluation. Results obtained by commercial kits and by in-house assays were indiscriminate in quality of performance in this study. CONCLUSION: To facilitate further quality assessment studies on the performance of GBV-C/HGV RNA detection, an international GBV-C/HGV RNA standard should be made available. Further efforts are required to optimize GBV-C/HGV RT-PCR.

[Prevalence of antibodies against hepatitis A in school children]. / Prevalencia de anticuerpos anti-hepatitis A en escolares en la década actual.

BACKGROUND: As sanitary conditions of a population improve, hepatitis A virus infection occurs at higher ages, thus decreasing the prevalence of antibodies against the virus. In the eighties, the prevalence of antibodies among children was 97% and depended on the socioeconomic level. AIM: To assess the prevalence of antibodies against hepatitis A virus in school age children living in Valdivia. SUBJECTS AND METHODS: Two thousand three hundred thirty three school age children were studied. Total antibodies against hepatitis A virus were detected using an ELISA kit from Abbott. Children were stratified in age groups and school were classified as private, subsidized, municipal or foster homes. RESULTS: Antibodies were positive in 65% of children (59% in children aged 6 to 8 years old, 66% in children aged 9 to 11 years and 69% in children aged 12 to 15 years. In private schools, the prevalence was 26%, in subsidized schools the figure was 54%, in municipal schools 73% and in foster homes 91%. CONCLUSIONS: The general prevalence of antibodies against hepatitis A virus is higher in low socioeconomic level children. There is a global decrease in the prevalence of these antibodies in the last years.

Epidemiological study of viral hepatitis types A, B, C, D and E among Inuits in West Greenland.

A descriptive study was performed to evaluate the relative frequencies and molecular epidemiological features of viral hepatitis types A to E among the Inuit population in West Greenland. Serum samples were collected from 503 Inuits (186 males and 317 females; mean age 35 years; range 7-79 years) and were tested for markers of viral hepatitis infection. The hepatitis A prevalence averaged 54%, with a significant rise from 9% to 50% between the second and third decade of life. As for hepatitis B, 42% of the total study population showed serological evidence of current or past hepatitis B virus (HBV) infection and 7% were hepatitis B surface antigen (HBsAg) carriers. Among the carriers, 6% were also positive for hepatitis B e antigen (HBeAg), and HBV DNA could be detected in 49% of carriers by polymerase chain reaction. Typing of the HBV isolates revealed genomic group D in 83% (serotype ayw2) and group A in 17% (serotype adw 2). Less than 1% of the study population had antibodies to the hepatitis C virus. None were positive for HCV RNA. Serological evidence of hepatitis D infection was found in 7% of those with hepatitis B helper virus infection markers and in 40% of the HBsAg carriers. As for hepatitis E, 3% of the Inuits showed reactivity in an enzyme immunoassay that detected hepatitis E virus antibody. HEV RNA could not be detected.

[Cross reactions of patients with acute dengue fever to tick-borne encephalitis]. / Kreuzreaktivität von Patientenseren mit akutem Dengue-Fieber mit Frühsommer-Meningo-Enzephalitis-Tests.

Sera from 20 patients with acute dengue fever were tested on their cross reactivities to other flaviviruses, especially against tick-borne encephalitis (TBE). One of the test systems used, indirect immunofluorescence (IIFT), was shown to exhibit strong cross reactivity. The reactivity pattern of sera from patients with pre-existing vaccine-induced antibodies against TBE or yellow fever was found similar to dengue secondary antibody response. In plaque reduction neutralization tests (PRNT) no cross reactions between different flaviviruses were found. The results show that PRNT is the most specific test system for differentiation of flavivirus antibodies.

Diagnosis of tick-borne encephalitis: evaluation of sera with borderline titers with the TBE-ELISA.

Tick-borne encephalitis (TBE) is a member of the Flaviviridae family. Strong cross-reactions can occur between members of this family, so that it may be difficult to diagnose specific flavivirus infections, especially when tests with frequent cross-reactions e.g. ELISA tests are used. We tested 238 sera with borderline titers for TBE using the indirect immunofluorescence or neutralization test for other flaviviruses (yellow fever, dengue, West Nile) to detect cross-reactions due to other flavivirus infections or flavivirus vaccination. Only one serum reacted against all the flaviviruses tested, indicating cross-reactivity due to infection with any of the flaviviruses. Two other sera exhibited low antibody titers against yellow fever, which could be confirmed by the neutralization test, indicating recent yellow fever vaccination. None of the other sera reacted at all against any of the flaviviruses tested in the tests used, which indicates false positive reactions with the TBE-ELISA. Sera with borderline titers in the TBE-ELISA in particular should be retested using other test systems (preferably neutralization) and for other flaviviruses (yellow fever, dengue, West Nile) to detect cross-reactions and to confirm positive results.

High immunogenicity and good tolerability of a new hepatitis A vaccine candidate.

Immunogenicity and tolerability of a new formalin-inactivated, alum-adjuvanted whole virus vaccine against hepatitis A (VAQTA, MSD, West Point, USA) were evaluated by immunizing 52 healthy, anti-HAV negative volunteers with a 1 ml dose. A booster dose was given 6 months later. In these young adult vaccinees [27 males and 25 females, 19-34 (mean 26) years of age] VAQTA proved to be well tolerated and highly immunogenic. Two weeks after administration of one vaccine dose, all but one of the recipients (98%) had anti-HAV concentrations above the presumed minimum protective level of 10 IU l-1 with a geometric mean concentration (GMC) of 165 IU l-1. After 4 weeks, a 100% seroconversion rate could be demonstrated with a fourfold increase of the GMC to 728 IU l-1. Six months after vaccination, all but one of the 50 volunteers coming back for booster (98%) showed anti-HAV levels within the protective range. The antibody concentrations had decreased in the majority of vaccinees to a GMC of 362 IU l-1. The booster dose given at that time was shown to be very effective, leading to a pronounced rise of anti-HAV levels in all recipients with a 17-fold increase of the GMC to 6040 IU l-1. Six months after the booster, all vaccinees were still seropositive with a GMC of 3444 IU l-1. Higher antibody levels were found in females, the difference being significant 4 weeks and 6 months after vaccination and 4 weeks after booster. No serious local or systemic adverse reactions were observed.

Improvement of virus safety of a S/D-treated factor VIII concentrate by additional dry heat treatment at 100 degrees C.

In order to increase the virus safety of a solvent/detergent-treated Factor VIII concentrate in regard to non-lipid coated viruses and to respond to the continuous discussion about reports on hepatitis A transmission by Factor VIII preparations, we have investigated the effect of a terminal dry heat treatment (30 min 100 degrees C) on HAV and various other viruses. By this treatment Hepatitis A virus was inactivated below detectable level after a few minutes (> 5.3 log10). Other RNA viruses such as the Human Immunodeficiency Virus (> 6.6 log10), bovine viral diarrhoea virus (> 6.6 log10) and vesicular stomatitis virus (> 5.8 log10) were also inactivated below detectable level. Pseudo rabies virus and reovirus Type 3 are inactivated by 5.7 and > 6.0 log10, respectively. SV40 and bovine parvo virus showed significant resistance to dry heat treatment. We conclude that the involvement of two strong virus inactivation steps, acting by different mechanisms, improves the virus safety of Factor VIII concentrates without destroying the Factor VIII activity. Moreover, the terminal 100 degrees C heat treatment for 30 min represents an effective measure to inactivate non-lipid enveloped viruses, in particular hepatitis A, which is resistant to solvent/detergent treatment.

Relative importance of the enterically transmitted human hepatitis viruses type A and E as a cause of foreign travel associated hepatitis.

Hepatitis contracted during a stay abroad may be caused by a wide range of pathogens including viruses, bacteria, protozoa or helminths. In many cases, the etiological agent primarily infects other target organs and tissues, involving the liver either as part of a disseminated infection or secondarily to mechanical biliary tract obstruction. The article focuses on enterically transmitted hepatitis caused by the primarily hepatotropic human hepatitis viruses type A and E and discusses their importance in travel-related disease.

Activation of a heterogeneous hepatitis B (HB) core and e antigen-specific CD4+ T-cell population during seroconversion to anti-HBe and anti-HBs in hepatitis B virus infection.

Overcoming hepatitis B virus infection essentially depends on the appropriate immune response of the infected host. Among the hepatitis B virus antigens, the core (HBcAg) and e (HBeAg) proteins appear highly immunogenic and induce important lymphocyte effector functions. In order to investigate the importance of HBcAg/HBeAg-specific T lymphocytes in patients with acute and chronic hepatitis B and to identify immunodominant epitopes within the HBcAg/HBeAg, CD4+ T-cell responses to hepatitis B virus-encoded HBcAg and HBcAg/HBeAg-derived peptides were studied in 49 patients with acute and 39 patients with chronic hepatitis B. The results show a frequent antigen-specific CD4+ T-cell activation during acute hepatitis B infection, a rare HBcAg/HBeAg-specific CD4+ T-cell response among HBeAg+ chronic carriers, and no response in patients with anti-HBe+ chronic hepatitis. An increasing CD4+ T-cell response to HBcAg/HBeAg coincides with loss of HBeAg and hepatitis B virus surface antigen (HBsAg). Functional analysis of peptide-specific CD4+ T-cell clones revealed a heterogeneous population with respect to lymphokine production. Epitope mapping within the HBcAg/HBeAg peptide defined amino acids (aa) 1 to 25 and aa 61 to 85, irrespective of the HLA haplotype, as the predominant CD4+ T-cell recognition sites. Other important sequences could be identified in the amino-terminal part of the protein, aa 21 to 45, aa 41 to 65, and aa 81 to 105. The immunodominant epitopes are expressed in both proteins, HBcAg and HBeAg. Our findings lead to the conclusion that activation of CD4+ T lymphocytes by HBcAg/HBeAg is a prerequisite for viral elimination, and further studies have to focus on the question of how to enhance or induce this type of T-cell response in chronic carriers. The immunodominant viral sequences identified may have relevance to synthetic vaccine design and to the use of peptide T-cell sites as immunotherapeutic agents in chronic infection.